Highly active hydrodesulfurization (HDS) catalysts have been prepared successfully through a molecular approach using well-defined Strandberg P-Mo-Ni polyoxometalates (POMs) as superior precursors. The hand-picked POMs significantly facilitated not only the formation of highly dispersed Ni-Mo species but also the formation of abundant and accessible NiMoS active sites at lower sulfidation temperatures, thereby resulting in a remarkable activity improvement in comparison with reference catalysts prepared with conventional precursors. Characterization results revealed the multidirecting effects of the POMs component and structure on the morphology and composition of the species in the NiMoS active phase and the evolution of precursors during the catalyst preparation simultaneously. The bottom-up POMs-based preparation methodology provides a better understanding of HDS catalyst structure and performance, thus further shedding light on the rational design and controllable fabrication of efficient HDS catalysts. (C) 2017 Elsevier Inc. All rights reserved.